Method to QC or other departments as needed. At

Method
Development & Validation of Metformin & Emphagliflozine dosage forms by
RPHPLC

 

Student: B.Jaffar Hussain 

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Reg.No14Q21S0702

Guige G.Somasekhar

 

CHAPTER-1

INTRODUCTION

 

Pharmaceutical
analysis simply means analysis of pharmaceuticals. Webster’ dictionary defines
a pharmaceutical is a medical drug. A more appropriate term for a
pharmaceutical is active pharmaceutical ingredient (API) or active ingredient
to distinguish it from a formulated product or drug product is prepared by
formulating a drug substance with inert ingredient (excipient) to prepare a
drug product that is suitable for administration to patients. Research and
development (R) play a very comprehensive role in new drug development
and follow up activities to ensure that a new drug product meets the
established standards is stable and continue to approved by regulatory
authorities ,assuring that all batches of drug product are made to the specific
standards utilization of approved ingredients and production method becomes the
responsibility of pharmaceutical analysts in the quality control (QC) or
quality assurance department . The methods are generally developed in an
analytical R department and transferred to QC or other departments as
needed. At times they are transferred to other divisions.

By now it should
be quite apparent that pharmaceutical analysts play a major role in assuring
the identity, safety, efficacy, and quality of drug product, safety and
efficacy studies required that drug substance and drug product meet two critical
requirements.

1.                 
Established identity and purity.

2.                 
Established bio
availability/dissolution.

 

 

 

Chapter:
3 DRUG PROFILE

 

           Empagliflozin

 

 

Empagliflozin
is a sodium glucose co-transporter-2 (SGLT-2) inhibitor
indicated as an adjunct to diet and exercise to improve glycemic control in
adult patients with type 2 diabetes. SGLT2 co-transporters are responsible for
reabsorption of glucose from the glomerular filtrate in the kidney. The
glucuretic effect resulting from SGLT2 inhibition reduces renal absorption and
lowers the renal threshold for glucose, therefore resulting in increased
glucose excretion. Additionally, it contributes to reduced hyperglycaemia and
also assists weight loss and blood pressure reduction.

Categories:

·        
Drugs
Used in Diabetes

·        
Alimentary
Tract and Metabolism

·        
Blood
Glucose Lowering Drugs, Excl. Insulins

Weight:  450.91

Chemical Formula:
C23H27ClO7

IUPAC Name:
(2S,3R,4R,5S,6R)-2-4-chloro-3-({4-(3S)-oxolan-3-yloxyphenyl}methyl)phenyl-6-(hydroxymethyl)oxane-3,4,5-triol

 

 

Chapter:
4  REVIEW OF LITERATURE

 

·        
K.S.
LAKSHMI et.al.. A
simple, sensitive and rapid reverse phase high performance liquid
chromatographic method was developed for the estimation of Metformin Hcl (MET)
and Pioglitazone (PIO) in pure and in pharmaceutical dosage forms. A Gemini C18
column (150×4.6mm, 5µ) was used with a mobile phase containing a mixture of
Acetonitrile and Ammonium Acetate buffer (pH-3) in the ratio of 42: 58. The
flow rate was 0.3ml/min and effluents were monitored at 255nm and eluted at
5.17min (MET) and 8.1min (PIO). Calibration curve was plotted with a range from
0.5-50 µg/ml for MET and 0.3-30 µg/ml for PIO. The assay was validated for the
parameters like accuracy, precision, robustness and system suitability
parameters. The proposed method can be useful in the routine analysis for the
determination on metformin and pioglitazone in pharmaceutical dosage forms.

·        
Manasa
et al.. In the present study, two analytical methods were developed for
the estimation of Dapagliflozin in API. Method A: RPHPLC method, Method B: UV
spectroscopic method. In method A, the drug showed linearity in the range of
25-150µg/ml with a correlation coefficient (r2 ) of 0.999, where as in method
B, the linearity range was found to be 1-5µg/ml with a correlation coefficient
of (r2 ) 0.999. Both the methods were validated for different validation
parameters such as linearity, accuracy, precision, detection limit,
quantitation limit, robustness and ruggedness and the results were found to be
within the acceptance limits as per the guidelines of International Conference
on Harmonization (ICH).

·        
Kavitha.
K. Y et al.. A simple, RP-HPLC method was established for
determining linagliptin and metformin in pharmaceutical formulations.
Linagliptin , metformin and their degradation products were separated using C8
column with Acetonitrile: Water: Methanol (25:50:25 (v/v/v) to pH 4.1 with 0.1%
orthophosphoric acid as the mobile phase. Detection was performed at 243 nm
using a diode array detector. The method was validated using ICH guidelines and
was linear in the range 5-30µg/ and 10-100 µg /ml for linagliptin and metformin
respectivily. Good separation of both the analytes and their degradation
products was achieved using this method. The developed method can be applied
successfully for the determination of linagliptin and metformin.

 

 

 

 

 

 

Chapter:
8.0 RESULTS AND DISCUSSION

 

8.1. Solubility Studies

These
studies are carried out at 25 0 C

METFORMIN:

soluble in methanol and in water, very slightly soluble in
phosphate buffer.

 

Chapter: 9.0 VALIDATION

 

9.1 System
suitability

Standard solutions were
prepared as per the test method and injected into the chromatographic system.
The system suitability parameters like theoretical plates, resolution and
asymmetric factor were evaluated.

1.   
The % RSD for the retention times of METFORMIN and EMPAGLIFLOZIN Peaks
from 6 replicate   injections of each
Standard solution should be not more than 2.0 %

2.         The % RSD for the peak area responses of
METFORMIN and EMPAGLIFLOZIN peaks from 6 replicate injections of each standard
solution should be not more than 2.0%. 

3.   The number of theoretical plates (N) for the METFORMIN
and EMPAGLIFLOZIN peaks is not less than
2000.

4.
  The Tailing factor (T) for the METFORMIN
and EMPAGLIFLOZIN peak is not more than 2.0.  

Observation   

The % RSD for the
retention times and peak area of METFORMIN and EMPAGLIFLOZIN were found to be
less than 2%. The plate count and
tailing factor results were found to be satisfactory and are found to be within
the limit. 

 

 

Chapter: 10 Discussion

 

                 A simple and selective LC
method is described for the determination of Metformin and
empagliflozin in tablet dosage forms. Chromatographic separation was achieved on
a c18 column using mobile phase consisting of a mixture of 50
volumes of methanol and 50 volumes of 
phosphate buffer with detection of 255 nm. Linearity was
observed in the range 60-140 µg /ml for Metformin (r2
=0.997) and 3-7µg /ml for empagliflozin (r2
=0.995) for the amount of drugs estimated by the proposed methods was in good
agreement with the label claim.